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Title: Molecular architecture of fungal cell walls revealed by solid-state NMR

Journal Article · · Nature Communications

The high mortality of invasive fungal infections, and the limited number and inefficacy of antifungals necessitate the development of new agents with novel mechanisms and targets. The fungal cell wall is a promising target as it contains polysaccharides absent in humans, however, its molecular structure remains elusive. Here we report the architecture of the cell walls in the pathogenic fungus Aspergillus fumigatus. Solid-state NMR spectroscopy, assisted by dynamic nuclear polarization and glycosyl linkage analysis, reveals that chitin and α-1,3-glucan build a hydrophobic scaffold that is surrounded by a hydrated matrix of diversely linked β-glucans and capped by a dynamic layer of glycoproteins and α-1,3-glucan. The two-domain distribution of α-1,3-glucans signifies the dual functions of this molecule: contributing to cell wall rigidity and fungal virulence. This study provides a high-resolution model of fungal cell walls and serves as the basis for assessing drug response to promote the development of wall-targeted antifungals.

Research Organization:
Univ. of Georgia, Athens, GA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES). Chemical Sciences, Geosciences, and Biosciences Division
Grant/Contract Number:
SC0015662
OSTI ID:
1511439
Journal Information:
Nature Communications, Vol. 9, Issue 1; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 141 works
Citation information provided by
Web of Science

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Chitinous polymers: extraction from fungal sources, characterization and processing towards value‐added applications journal May 2020
Atomic resolution of cotton cellulose structure enabled by dynamic nuclear polarization solid-state NMR journal November 2018
Molecular architecture of softwood revealed by solid-state NMR journal October 2019
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Longitudinal Relaxation Optimization Enhances 1 H‐Detected HSQC in Solid‐State NMR Spectroscopy on Challenging Biological Systems journal February 2019
Circulating (1→3)-β-D-glucan Is Associated With Immune Activation During Human Immunodeficiency Virus Infection journal March 2019
Molecular architecture of softwood revealed by solid-state NMR text January 2019
Aspergillus fumigatus and Aspergillosis in 2019 journal November 2019
The puzzling construction of the conidial outer layer of Aspergillus fumigatus journal January 2019
Integration of electron microscopy and solid-state NMR analysis for new views and compositional parameters of Aspergillus fumigatus biofilms journal February 2019
FGB1 and WSC3 are in planta‐ induced β ‐glucan‐binding fungal lectins with different functions journal February 2019
The melanization road more traveled by: Precursor substrate effects on melanin synthesis in cell-free and fungal cell systems journal November 2018
Molecular architecture of softwood revealed by solid-state NMR. text January 2019